By Liz Highleyman
Prior research has shown that HIV positive people coinfected with hepatitis C tend to experience more rapid liver disease progression and are less likely to respond to interferon-based therapy compared to individuals with chronic hepatitis C alone.
Insulin resistance -- a precursor to diabetes -- is also a predictor of poorer treatment response in patients with HCV alone, but this association has not been extensively evaluated in people with HIV/HCV coinfection.
In a prospective observational study, Paola Nasta and colleagues from the University of Brescia in Italy looked at the correlation between HCV RNA viral load, hepatitis C treatment response, and insulin resistance in 107 HIV/HCV coinfected patients.
Most participants (about 85%) were men and the average age was about 43 years. Half had hard-to-treat HCV genotypes 1 or 4, and nearly 60% had advanced liver fibrosis (Metavir stage F3-F4). Almost all patients (93%) were taking combination antiretroviral therapy (ART).
Participants received a hepatitis C treatment regimen consisting of 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin. HCV viral load was measured at baseline and then every 3 months. The researchers assessed sustained virological response (SVR), or continued undetectable HCV RNA 24 weeks after finishing therapy.
Insulin resistance was evaluated using the HOMA-IR (homeostasis model of assessment-insulin resistance) method, which is calculated based on fasting insulin level. At baseline, the average HOMA-IR score was 3.2; a score > 3.0 is typically considered the threshold for insulin resistance.
Results
- Overall, 44% of treated patients achieved SVR.
- In a multivariate analysis, the following 3 factors were significant independent predictors of sustained response:
- HCV genotypes 1 or 4 (vs 2 or 3): adjusted odds ratio 0.10, or 90% less likely to achieve SVR;
- Baseline HCV RNA < 400.000 IU/mL: adjusted odds ratio 3.08, or about 3 times more likely to respond;
- HOMA-IR < 3.0: adjusted odds ratio 3.5, or 3.5-fold more likely to respond.
- Advanced liver fibrosis, blood lipid levels, and HIV viral load did not significantly affect likelihood of SVR.
- Lower HOMA-IR was also significantly associated with lower HCV viral load:
- HCV RNA < 6 log: median HOMA-IR score 2.9;
- HCV RNA >6 log: median HOMA-IR score 3.3.
These findings led the investigators to conclude, "A linear relationship was detected between HOMA-IR and hepatitis C viral load in HIV/HCV coinfected [patients] regardless viral genotype."
"This result could contribute to explain[ing] the role of insulin-resistance on the anti-HCV treatment outcome in HIV/HCV coinfected persons," they suggested.
University of Brescia, Brescia, Italy.
10/5/10
Reference
P Nasta, F Gatti, and F Borghi. Insulin Resistance is Associated with Hepatitis C Viremia and Reduces the Success of Peginterferon alfa2a Plus Ribavirin in HIV/HCV Co-Infected Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-1683.
Source: hivandhepatitis.com
